First off, this thread seems to bring out the most "reddit-like" posts on HN.
If you've come here to shoot a funny one-liner comment, please reconsider - the point is discussion, not karma farming.<p>Now, on the topic itself - I really wonder about the safety profile of these. While this selectively inhibits only RARα and is thus "biased" towards mostly acting on testes, it could also have side-effects - and while the effect might not be pronounced yet, with long term use it definitely could be, especially if all the RARα receptors get inhibited (will beta and gamma pick up the slack? what is it going to cause?).<p>Considering the 99% effectiveness claim and the method of action, I wonder if the embryos in that 1% case can even survive.
I was curious about the mechanism.<p><a href="https://www.nature.com/articles/s43856-025-00752-7" rel="nofollow">https://www.nature.com/articles/s43856-025-00752-7</a><p>> YCT-529 works by interfering with vitamin A signaling necessary for sperm production and fertility.<p>> The importance of dietary vitamin A and retinoid signaling for male germ cell development and differentiation has been recognized for many years6. All trans-retinoic acid (Fig. 1a) is an active metabolite of vitamin A that exerts its function, at least partly, by binding to retinoic acid receptors (RARs). The RARs α, β, and γ, are encoded by the Rara, Rarb, and Rarg genes in mice, and Rarα and Rarγ have been validated as contraceptive targets by genetic knockouts resulting in male sterility7,8. Notably, the effects on spermatogenesis in the absence of RARα most resemble the loss of RAR signaling in vitamin A deficiency, and the mice are otherwise normal7,8. Further, the effects on spermatogenesis in animals treated orally with the dual RARα/RARγ antagonist BMS-189453 (Fig. 1a, b) closely phenocopied the absence of RARα function. Importantly, the resulting male sterility is reversible9,10,11. We, therefore, wished to identify RARα−selective inhibitors for potential male non-hormonal contraception. Our study describes the development of YCT-529, a highly selective RARα antagonist that reduces sperm counts in mice and non-human primates. Mating studies with male mice treated with 10 mg/kg/day for 4 weeks show that YCT-529 is 99% effective in preventing pregnancies and that the mice fully regain fertility after drug cessation.
We had alpha-blockers for a long time now, which prevents ejaculation but not orgasm; read: it can completely block the emission phase of ejaculation, while orgasmic function is retained.<p>Example: Silodosin.<p>You need to experiment with it. Sensitive clinical trials measured rates as high as 90-99%.<p>It is entirely non-hormonal. It does not affect libido (rarely), while hormonal male contraceptives do, and it is reversible upon cessation, without any delay, unlike hormonal male contraceptives.
There is a hormone-free option for men today <a href="https://en.wikipedia.org/wiki/Heat-based_contraception" rel="nofollow">https://en.wikipedia.org/wiki/Heat-based_contraception</a>. It's not widely known but has solid science backing it up and even though the wikipedia article claims no long term studies were done, in the 1930s IIRC there was a series of tests done in India and it had men conceive healthy children after a couple of years of using this method. And there have been other long term studies suggesting the same absence of long-term effects if anyone is interested I looked them up a while ago and could go looking for the links.
RARα pathway operates in cell development eg of blood cells and in apoptosis, implicated in some cancers.<p>Long-term safety seems doubtful. Offspring could be affected. In a rational world there would be no volunteers for the trials.
This is important, as women coercing men or ignoring their consent regarding pregnancy is not uncommon.<p><a href="https://en.m.wikipedia.org/wiki/Forced_fatherhood" rel="nofollow">https://en.m.wikipedia.org/wiki/Forced_fatherhood</a>
> Both mice and non-human primates fully regained fertility after stopping the drug. Mice regained fertility within six weeks, and non-human primates fully recovered their sperm count in 10-15 weeks.<p>Great recurring source of revenue for the drug company!<p>Though I'm more interested in feral animals like dogs. It looks like this drug may work on dogs too? If so, it would be a huge boon for cities and villages in India.
I'm sure it's illegal for a woman to secretly swap out her boyfriend's medicine for a placebo, but good luck proving it happened in court.
From big pharma, yes.<p>But their so called "solutions" seem to become ever more destructive long term.<p>Neem is a natural alternative that has been used for a long time.
One concern I might have is that I’ve heard (and Wikipedia confirms, though with caveats[1]) that ejaculation can help avoid prostate cancer.<p>“These [studies] suggest that frequent ejaculation after puberty offers some reduction of the risk of prostate cancer.”<p>I think we need more/bigger studies to get a handle on how big the effect is though.<p>[1] NSFW warning - this is a Wikipedia article with a picture of a guy ejaculating riiiiight at the top: <a href="https://en.m.wikipedia.org/wiki/Ejaculation#Health_issues" rel="nofollow">https://en.m.wikipedia.org/wiki/Ejaculation#Health_issues</a>
This is one of the annoying things about life. Testosterone effectively already does this and is quite safe. It's just that society is not comfortable with men taking steroids for no particularly good reason.